1. Field of the Invention
The invention generally relates to radiochemical processing and more particularly to a process for processing radiochemical materials for medical applications.
2. Background Information
Several medical and industrial technologies drive world-wide demand for 153Gd. By far, the largest 153Gd demand is for Single Photon Emission Computed Tomography, or SPECT, scanners that are used for the diagnosis and monitoring of neurological disorders, cardiac blockages or abnormalities, and primary and metastasized cancer tumors. 153Gd has also been shown to be a superior tool for localizing lymph nodes during biopsies, and has industrial applications measuring the strength and integrity of structural materials and piping systems.
Determining gamma ray attenuation in the body is difficult due to the presence of multiple organ and tissue types, all of which have different attenuation coefficients. Additionally, these organs and tissues vary in size and density from patient to patient. To correct for these differences, the transmission of gamma rays through the patient from a source of known strength is measured at several angles to provide spatially specific attenuation coefficients for tissues within each patient.
153Gd is an isotope for use in such attenuation corrections. 153Gd decays via electron capture and emits two prominent photons at 97.43 keV and 103.18 keV, which are energetic enough to move through the body of the patient, but expose the patient to as little dose as possible. With a half life of 240.4±1.0 days, 153Gd is also long-lived enough to be useful in a clinical setting. Beta particles and lower-energy gamma rays and x-rays from 153Gd are easily blocked with a filter (e.g. copper), and the additional radioactive dose to the patient above that of the in vivo radioisotope is minimal.
153Gd is also ideal for localizing sentinel lymph nodes during biopsies. While another radioisotope attached to a tumor-seeking biological marker pinpoints the lymph node in question, a 153Gd line source is used to determine the physical outline of the patient, allowing the determination of the precise node location for the surgeon. The 153Gd line source is superior to manual body imaging and a 57Co-flood source. The commercially available Lixi Profiler® is an example of 153Gd use in industry. The profiler is a hand-held device that uses 153Gd gamma rays to non-destructively interrogate wood, rubber, composite materials, welds, and pipe wails for defects or corrosion. It is estimated that the current demand for 153Gd is approximately 300 Ci per year.
Despite the high demand for 153Gd in the United States, there has not been a domestic 153Gd supplier for many years. This in part is due to the problems associated with the existing separation technologies. Because the 153Gd must be on the order of 99.999% radiochemically pure for medical and industrial applications, extensive chemical processing of the irradiated target is necessary. Additionally, because of the intense radioactivity of the irradiated target, processing must be conducted in radiological hot cells, which have special safety restrictions (e.g. flammability loading) that can limit potential chemical purification methods.
Purification of 153Gd from an irradiated, natural europium target requires multiple steps, also referred to as “strikes”. The first purification step is heavily limited by the intense dose from the radioactive europium isotopes produced during the neutron irradiation. Indeed, the europium activity is so high that separations techniques such as ion exchange and liquid-liquid extraction are usually contraindicated for the first purification step because the organic polymers and solvents suffer substantial radiation-induced degradation and lose efficacy.
Fortunately, a very effective first strike can be implemented by exploiting the solubility difference between Eu(II)SO4 and Ln(III)2(SO4)3, where Ln is the general symbol for an element in the lanthanide series (elements 57La through 71Lu, inclusive). Europium is one of a few lanthanides that can be reliably reduced to the Ln2+ state while, under the same conditions, gadolinium remains as Ln3+. EuSO4 has a Ksp on the order of 10−6 to 10−8, depending on the background electrolyte, yielding a solubility range of approximately 0.25 to 0.025 g/L. Eu2(SO4)3, Gd2(SO4)3, and Sm2(SO4)3.8H2O all have solubilities greater than 21 g/L, allowing for separation from EuSO4(s) by factors between 84 and 840. Conveniently, the reduction and precipitation of the europium can be monitored visually during experiments: Eu3+ in chloride solution is colorless, Eu2+ is yellow, the EuSO4 solid is a fine white crystal, and Eu2(SO4)3 is light pink.
The quality and yield of the Eu(II)SO4 precipitate is influenced by several factors, including, but not limited to: reduction methods, the reduction medium, europium concentration, sulfate concentration, reaction time, impurities, and temperature. Depending on conditions, a single reduction and precipitation pass can produce EuSO4 yields as high as 99.9%.
Eu3+ can be reduced via electrochemical reduction, photo-reduction, and, if organics that scavenge oxidizing radiolysis products are present, gamma-ray irradiation. Eu3+ reduction can also be accomplished with an amalgamation process that Mel'nik and coworkers named “cementation”, where an alkali metal amalgam is used to reduce europium first to the divalent state and then to the metal amalgam, Eu0(Hg). Various metals and metal amalgams (e.g. magnesium, sodium, and europium), as well as metal hydrides and nitrogenous reductants, have been tested for Eu3+ reduction. Metallic zinc and metal amalgams show superior results (greater than 99.7% EuSO4 precipitation) over the nitrogenous and metal hydride reductants (0% EuSO4 precipitation). The efficiency of zinc metal and zinc amalgam methods make them two of the most common Eu3+ reduction methods, either in batch or column form. The governing electrochemical equations are shown in equations (2) and (3).2Eu3++2e−→2Eu2+ E°=−0.36 V  (2a)Zn0→Zn2++2e− E°=0.7618 V  (2b)Zn(Hg)→Zn2++2e− E°=0.7628 V  (2c)2Eu3+(aq)+Zn0(s)→2Eu2+(aq)+Zn2+(aq) E°=0.4018 V  (3a)2Eu3+(aq)+Zn(Hg)(s)→2Eu2+(aq)+Zn2+(aq) E°=0.4018 V  (3b)
A zinc-based reductor column is mechanically the simplest reduction method to implement in a radiological hot cell environment. No electrochemical cells or electrodes are needed and, in the column form, no filtration of the zinc metal from the lanthanide solution is necessary.
Although the zinc reduction method is simple and straightforward mechanically, it can have chemical products that present unacceptable hazards in a hot cell environment. As shown in equations (4) and (5), the use of metallic zinc in an aqueous environment generates vigorous hydrogen production and bubbling stemming from the redox reaction of the metallic zinc and hydrated protons in solution.Zn0→Zn2++2e− E°=0.7618 V  (4a)2H++2e−→H2 E°=0.00 V  (4b)Zn0(s)+2H3O+→Zn2++H2(g)+H2O E°=0.7618 V  (5)
If used in a column, the hydrogen gas bubbles produced in equation (5) can isolate the europium solution from the zinc surface, preventing full reduction. The hydrogen gas production also creates a significant fire hazard and, as such, is not permitted within radioactive hot cells. One alternative to europium reduction in acidic solutions is to use basic solutions, but this is impractical, as rare earth hydroxides are very insoluble. Using zinc amalgam prevents hydrogen generation in aqueous solutions, but creates a mixed mercury-radioactive waste that is difficult and costly to dispose of.
With a redox potential E°(III/II)=−0.36, Eu2+ is very easily oxidized to Eu3+. Exposure to atmospheric oxygen will oxidize Eu2+, via the following reaction:2Eu2+→2Eu3++2e− E°=0.36 V  (6a)½O2+H2O+2e−→2OH− E°=0.401 V  (6b)2Eu2+(aq)+½O2+H2O→2Eu3+(aq)+2OH− E°=0.761 V  (7)
EuSO4 precipitations are preferably performed under an inert cover gas. Reduction effectiveness and stability also depend on the solvent and background electrolytes. A water based solvent will cause some oxidation of Eu2+ in combination with light:Eu2+→Eu3++e− E°=0.36 V  (8a)H2O+e−→OH−+½H2 E°=−0.8277 V  (8b)Eu2++H2Ohv→Eu3++OH−+½H2 E°=−0.4677 (9)
Even though the value of E° for equation (9) is negative, and therefore not spontaneous from left to right, the addition of light provides the energy needed to allow excess hydrated protons to oxidize Eu2+. The presence of hydrated protons also encourages oxidation from Eu2+ to Eu3+, shown in equations (10) and (11).Eu2+→Eu3++e− E°=0.36 V  (10a)2H++2e−→H2 E°=0.00 V  (10b)Eu2+H3O+→Eu3++H2O+½H2 E°=0.36 V  (11)In general, background electrolytes with strong oxidizers, such as HNO3, must be avoided.
Europium concentration has a significant influence on reduction efficiency. Europium can be maintained in the reduced state for at least 10 to 15 minutes when it is present in concentrations above 10 mM. At tracer levels (˜10−10 M), oxygen scavengers are typically necessary to maintain the divalent oxidation state. Prior art experiments to determine the effects of process conditions on the recovery and punt of precipitated EuSO4 from a rare earth concentrate containing neodymium, samarium, europium, gadolinium, and terbium. In studies using 0.1 g of europium and 0.02 moles of H2SO4 as the sulfate source, a three-fold stoichiometric excess of zinc metal was required to obtain the maximum reduction and recovery of EuSO4, but the stoichiometric amount of zinc appeared to have no effect on EuSO4 purity. Eu2+ recovery increased with sulfate concentration until a stoichiometric ratio of 1:3 (Eu2+:SO42−) was reached, above which the europium purity dropped precipitously due to the precipitation of other Ln(III) sulfates. The sulfate must also be added after the europium has been reduced by a zinc column, or EuSO4 will precipitate on the column and possibly restrict column flow.
Reduction experiments using europium, zinc, H2SO4, and a batch testing method needed 60 to 90 minutes to reach maximum europium reduction and 60 to 90 minutes after the sulfate addition for maximum EuSO4 yield. Precipitation of EuSO4 from solution with significant amounts of other elements (such as dissolved ores that contain rare earths and iron) demonstrates reduction kinetics that are about three times slower than solutions containing only rare earths. Another study found that the purity and yield of the europium (II) sulfate vas improved when the sulfate was added at 1 mL/minute or less. The slower addition keeps the sulfate concentration lower at all times, preventing saturation conditions that can cause the precipitation of unwanted trivalent lanthanide sulfates. Additional gadolinium purification strikes fall into three categories: removal of the remaining ˜1% of the europium, removal of dissolved zinc, and removal of unwanted anions (e.g. SO42−) from solution.
A number of techniques have been used to remove the remaining europium from solution. Bray and Corneillie countered the difficulty of reducing and precipitating the small amount of europium left after the first strike by adding a reducible quantity of stable europium and repeating the reduction-precipitation reaction. This technique successfully removes much of the remaining radioactive europium, but it may also lower the overall gadolinium yield via co-precipitation.
Other common secondary europium strikes include reduction of europium followed by liquid-liquid extraction with organic solvents such as HDEHP, HEH(EHP), TTA, etc., and/or ion exchange Chromatography using resin beads impregnated with the aforementioned solvents. Ion exchange chromatography using a variety of complexants that exploit the Eu2+/Eu3+ charge difference has also been reported. Using long, pressurized ion exchange columns to exploit the lanthanide contraction is also possible, and provides a good separation for non-adjacent lanthanides like gadolinium and samarium, but stronger overlap for adjacent lanthanides like europium and gadolinium.
Zinc removal from gadolinium solutions is typically achieved via solvent extraction or precipitation of ZnS with H2S(g). Solvent extraction of zinc with Cyanex 925, a commercial phosphine oxide, has been reported to strip 99% of the aqueous zinc after five counter-current stages without the loss of rare earths. Removal of zinc from aqueous solution with hydrogen sulfide gas is a classic chemical method, shown in equation (12a). The Kspa for ZnS is 3×10−2 or 2×10−4, depending on the solid phase, which gives a maximum ZnS solubility above pH 2 of 0.17 g/L. Because ZnS is soluble if the pH is less than two, some amount of a soluble base must be added with the H2S(g) to counter the hydrochloric acid produced by the precipitation of ZnS (equation 12b).ZnCl2(aq)+H2S(g)→ZnS(g)+2HCl(aq)  (12a)HCl+OH−→Cl−+H2O  (12b)
The final purification step after all of the non-gadolinium rare earths and the zinc have been removed is to exchange unwanted anions in solution (e.g. leftover SO42−) for the anion used in the final gadolinium product (e.g. Cl− or NO3−). A standard chloride-form or nitrate-form anion exchange column is typically utilized for this step
While various attempts have been made to address the issues none have been completely successful. In some industrial processes, samarium and terbium impurities (products of that particular neutron irradiation scheme) are removed by HDEHP-nitric acid extraction chromatography and non-radioactive impurities are removed by cation exchange. The purified 153Gd is twice precipitated as Gd2(C2O4)3 and converted to Gd2O3. The gadolinium oxide is dissolved in 4 M nitric acid and heated to form a moist salt. The international producers report a 153Gd radiochemical purity of 99.997% (radiological contaminants are 2.8527×10−3% 151Gd, 4.9×10−6% 152Eu, and 5.1×10−6% 154Eu) and a specific activity of 73.79 Ci/g. What is needed therefore is an improved process that eliminates and/or reduces both the hazardous mercury and dangerous hydrogen gas generation. The present invention meets these needs.
Additional advantages and novel features of the present invention will be set forth as follows and will be readily apparent from the descriptions and demonstrations set forth herein. Accordingly, the following descriptions of the present invention should be seen as illustrative of the invention and not as limiting in any way.